Trial Targeting Gut Bacterial Androgen Production to Reverse Therapeutic Resistance to Abiraterone in Patients With Metastatic Prostate Cancer

Inclusion criteria

• Males aged 18 years of age and above.
• Prostate adenocarcinoma
• Absolute PSA ≥ 2.0 ng/mL at screening.
• PSA (+/- radiographic) progression after having been on abiraterone and prednisone for at least 12 weeks.
• Must be maintained on a GnRH analogue or have undergone orchiectomy.
• Participants must have a life expectancy ≥ 6 months
• Ability to swallow study medication tablets
• Willing to abstain from alcohol during and for 14 days after treatment with metronidazole
• Willing and able to collect urine and stool samples per protocol

Exclusion criteria

• Active infection or other medical condition that would make dexamethasone use contraindicated
• Any chronic medical condition requiring a higher systemic dose of corticosteroid
• Pathological finding consistent with small cell carcinoma of the prostate
• Has imminent or established spinal cord compression based on clinical findings and/or MRI.
• Chronic liver disease with Child-Pugh class C cirrhosis (see calculator in protocol)
• Bilirubin \>3x ULN or AST and ALT \>5x ULN
• Congenital prolonged QTc syndrome or QTc \> 500 msec (non-paced rhythm)
• History of pituitary or adrenal dysfunction
• Uncontrolled diabetes (Hemoglobin A1c \> 10%) or increasing doses of insulin within the past 4 weeks due to poorly controlled glucoses.
• Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational drug study
• Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
• Any uncontrolled major infection.
• Crohn's disease or ulcerative colitis.
• Known or suspected toxic megacolon and/or known small bowel ileus.
• Known allergy to any of the compounds under investigation.
• On antibacterial therapy within 30 days prior to administration of study treatment.
• Any condition or situation which, in the opinion of the investigator, would put the subject at risk, or interfere with the subject's participation in this study.